Antibiotics for Pneumonia: Short Course Is More Effective

Diana Phillips

July 09, 2019

For patients hospitalized with community-acquired pneumonia (CAP), more is not better when it comes to antibiotic therapy. In fact, it is likely worse, a study has shown.

Using data from a 43-hospital quality improvement consortium, Valerie M. Vaughn, MD, assistant professor of medicine at the University of Michigan Health System, Ann Arbor, and colleagues evaluated antibiotic prescriptions for the treatment of nearly 6500 adults with community-acquired pneumonia from 2017 to 2018.

More than two thirds of the patients received antibiotic courses that exceeded necessary durations. Typically linked to post-discharge oral stepdown therapy, the longer treatment courses did not improve patient outcomes, but did increase the risk for antibiotic-associated adverse events, the authors report in an article published online July 8 in Annals of Internal Medicine.

Antibiotics prescribed at discharge accounted for nearly half (49.5%) of total antibiotic days and nearly all (93.2%) of excess antibiotic days. That nearly all excess therapy resulted from antibiotics prescribed at discharge "highlights an urgent and unmet need for 'discharge stewardship,' or coordinated interventions to improve antibiotic prescribing at discharge," the researchers write. "It is notable that only 18% of patients received 0 or 1 day of antibiotics after discharge despite it being expected for 61.6%. Instead, the clock seemed to restart, given that 44.7% received full antibiotic courses (5, 7, or 10 days) after discharge."

The researchers based their assessment of sufficient antibiotic therapy on national guidelines that recommend antibiotic treatment duration on the basis of pneumonia classification, organism, and time to clinical stability. According to these criteria, the expected antibiotic duration for patients with CAP is at least 5 days (longer in cases where time to clinical stability was longer). The expected treatment duration for patients with healthcare-associated pneumonia (HCAP), Staphylococcus aureus, or a nonfermenting gram-negative bacillus is at least 7 days, the authors note.

Of the 6481 patients (median age 70.2 years) included in the analysis, 4747 had CAP and 1734 had HCAP. More than half (57.4%) had severe pneumonia, and 26.4% and 7.5%, respectively, had concurrent chronic obstructive pulmonary disease or a congestive heart failure exacerbation.

With respect to treatment duration, 67.8% of patients received excessive courses of antibiotics, including 71.8% of patients with CAP and 56.6% of patients with HCAP. Among those with CAP and HCAP, respectively, the median antibiotic treatment duration was 8 days and 9 days, and the respective median excess duration was 2 days and 1 day. "This led to 2526 excess days of treatment per 1000 patients hospitalized with pneumonia," the authors write.

The excess treatment duration is consistent with observations from prior studies and was not explained by differences in clinical stability or disease severity. "Indeed, most patients with CAP (86.7%) stabilized quickly and thus were candidates for 5 days of therapy, yet fewer than 24.7% received 5 (±1) days of therapy," the authors note.

Further, given that providers appeared to treat CAP and HCAP with similar durations of antibiotics, misdiagnosis of CAP as HCAP does not explain the excess treatment duration in patients with CAP. "Providers may not differentiate between CAP and HCAP because of the national movement away from the latter term or the difficulty with risk stratification at the point of care," the authors suggest.

In an analysis looking at characteristics associated with excess treatment duration, patients with sputum production were 7% more likely to have longer-than-needed antibiotic courses (rate ratio, 1.07; 95% confidence interval [CI], 1.02 - 1.13). Multivariable analyses linked having a respiratory culture or a nonculture diagnostic test, a longer hospital stay, high-risk antibiotic use in the prior 90 days, and CAP with higher rates of excess treatment. Not having total treatment duration documented at discharge was also linked to excess treatment.

"It is unclear whether hospitals with better documentation are more likely to appropriately treat patients (for example, due to stewardship initiatives) or whether documentation itself triggers a mindful moment that leads to improved treatment duration," the authors write. "Regardless, documentation is a core stewardship strategy, and hospitals should strive to improve it, particularly at discharge."

Academic hospitals also had lower rates of excess treatment, a finding the researchers say merits additional exploration. "Academic hospitals have more institutional support for stewardship and follow more of the Centers for Disease Control and Prevention's recommendations, which may explain this difference," they hypothesize. They note, however, that differences in antibiotic stewardship interventions related to treatment duration might contribute to variation across hospitals.

In adjusted analyses, excess treatment duration did not improve rates of 30-day mortality, readmission, or emergency department visits, but it did increase the likelihood of adverse events associated with antibiotic treatment. Among patients who were contacted by telephone 1 month post discharge, the odds of a patient-reported adverse event were 5% (CI, 2% - 8%) higher for each excess day of treatment. The most common adverse events were diarrhea, gastrointestinal distress, and mucosal candidiasis.

"This adds to growing literature that short-course therapy in pneumonia is safe and that longer durations are not just unnecessary but potentially harmful," the authors write. "Therefore, reducing excess treatment durations should be a top priority for antibiotic stewardship nationally."

The study findings have research and policy implications, the authors explain. "Specifically, the next iteration of CAP and HCAP guidelines should explicitly recommend (rather than imply) that providers prescribe the shortest effective duration, similar to recommendations made in the hospital-acquired and ventilator-associated pneumonia guidelines," they note.

Given that excess antibiotic prescribing continues despite national efforts to contain it, "future improvement may be more effective by focusing on discharge stewardship, including antibiotic documentation at discharge, and on patients with high rates of overuse, such as those with CAP," the authors recommend. They also advocate for the incorporation of antibiotics prescribed at discharge into national use metrics.

Acknowledging "change is scary and medicine is a conservative profession," the authors of an accompanying editorial stress that "we must overcome inertia and tradition and change practice when compelling evidence becomes available."

Doing so is essential in order to "live up to the expectations that our patients have for us and that we have for one another," write Brad Spellberg, MD, of the University of Southern California Medical Center in Los Angeles, and Louis B. Rice, MD, of Warren Alpert Medical School of Brown University in Providence, Rhode Island.

"After dozens of [randomized controlled trials] and more than a decade since the initial clarion call to move to short-course therapy, it is time to adapt clinical practice for diseases that have been studied and adopt the mantra 'shorter is better.'"

The findings of the current study add weight to this mantra, the editorialists write. "The cumulative evidence indicates that each day of antibiotic therapy beyond the first confers a decreasing additional benefit to clinical cure while increasing the burden of harm in the form of adverse effects, superinfections, and selection of antibiotic resistance," they state. "The question is, where do those 2 competing trends cross, such that continuing tilts the balance to harm over benefit? For community-acquired pneumonia, the data indicate net harm somewhere around 3 to 5 days of therapy for most patients."

In the face of continued underuse of short-term antibiotic therapy, the editorialists stress, "it is time for regulatory agencies, payers, and professional societies to align themselves with the overwhelming data and assist in converting practice patterns to short-course therapy."

Support for the Michigan Hospital Medicine Safety Consortium is provided by Blue Cross Blue Shield of Michigan (BCBSM) and Blue Care Network as part of the BCBSM Value Partnerships program. Multiple study coauthors report receiving support during the conduct of the study; see study disclosures for full details. Rice reports relationships with Zavante Pharmaceuticals and Macrolide, outside the submitted work. Spellberg reports relationships with Alexion, Paratek, TheoremDx, Acurx, Shionogi, and Merck, as well as other support from Motif, BioAIM, Mycomed, and ExBaq, outside the submitted work.

Ann Intern Med. Published online July 8, 2019. Abstract, Editorial

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